1. Field of the Invention
This invention relates to the purification of N-[N-(3,3-dimethylbutyl)-L-.alpha.-aspartyl]-L-phenylalanine 1-methyl ester (.alpha.-neotame) by resolution of the isomers of neotame.
2. Related Background Art
N-[N-(3,3-dimethylbutyl)-L-.alpha.-aspartyl]-L-phenylalanine 1-methyl ester (.alpha.-neotame) is a high potency dipeptide sweetener (about 8000.times. sweeter than sucrose) that has the formula ##STR1##
Its .beta.-isomer, N-[N-(3,3-dimethylbutyl)-L-.beta.-aspartyl]-L-phenylalanine 1-methyl ester (.beta.-neotame), has the structure ##STR2##
The chemical synthesis of .alpha.-neotame is disclosed in U.S. Pat. No. 5,480,668, U.S. Pat. No. 5,510,508 and U.S. Pat. No. 5,728,862, the disclosure of each of which is incorporated by reference herein. U.S. Pat. Nos. 5,510,508 and 5,728,862 describe the conventional synthesis of .alpha.-neotame by hydrogenation of a mixture of aspartame and 3,3-dimethylbutyraldehyde with a catalyst such as Pd on carbon.
A number of other synthetic routes to neotame have been explored. Certain of these routes, for example, the coupling of phenylalanine methyl ester to neo-aspartic anhydride as disclosed in U.S. Pat. No. 6,077,962, and methods which employ Z-aspartame (.alpha.- and .beta.-mixture) as a starting material, as disclosed in U.S. Pat. No. 5,302,743 and JP 60-075497, do not yield pure .alpha.-neotame. In fact, both the desired .alpha.-isomer and the undesirable .beta.-isomer of neotame are obtained. Since .alpha.-neotame is mainly employed in foods for human consumption, it is extremely important that .alpha.-neotame exist in a highly purified state. Thus, it is clear that there is a need for a purification strategy which selectively produces the pure .alpha.-isomer of neotame.